Acute endotoxemia in rats induces down-regulation of V2 vasopressin receptors and aquaporin-2 content in the kidney medulla

BACKGROUND: Endotoxemia can lead to fluid metabolism alterations despite unchanged or elevated plasma vasopressin (VP) levels, suggesting a refractoriness of the kidney to the effect of the peptide. To test this hypothesis, we examined the effect of lipopolysaccharide (LPS) injection on the expression of V2 receptors and aquaporin-2 in the kidney. METHODS: Plasma VP and urine osmolality, and binding of [3H]VP to kidney membranes, Western blot, and immunohistochemical analysis of aquaporin-2, in situ hybridization for V2 VP receptors and cytokines mRNAs were measured in the kidney 3 to 24 hours after LPS injection, 250 microg/100 g, intraperitoneally. RESULTS: LPS injection caused prolonged decreases in urine osmolality (up to 24 hours) without significant changes in plasma levels of sodium or VP. This was associated with marked decreases in V2 VP receptor mRNA and VP receptor number in the kidney, which were evident for up to 12 hours after LPS injection. Aquaporin-2 in kidney inner medulla was also reduced by about 50%. LPS induced interleukin (IL)-1beta in the kidney medulla by 3 hours, reached maximum at 6 hours, and started to decline by 12 hours, while it increased IL-6 mRNA significantly only at 3 hours. Interleukin mRNA expression was absent in kidneys of control rats. In vitro incubation of kidney medulla slices with IL-1beta reduced VP binding. CONCLUSION: The inflammatory response to acute endotoxemia down regulates V2 VP receptors and aquaporin-2 of the kidney inner medulla resulting in prolonged impairment of the renal capacity to concentrate urine.     

Lobeline analogs with enhanced affinity and selectivity for plasmalemma and vesicular monoamine transporters

Lobeline attenuates the behavioral effects of psychostimulants in rodents and inhibits the function of nicotinic receptors (nAChRs), dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Monoamine transporters are considered valid targets for drug development for the treatment of methamphetamine abuse. In the current study, a series of lobeline analogs were evaluated for affinity and selectivity at these targets. None of the analogs was more potent than nicotine at the [3H]methyllycaconitine binding site (alpha7* nAChR subtype). Lobeline tosylate was equipotent with lobeline in inhibiting [3H]nicotine binding but 70-fold more potent in inhibiting nicotine-evoked 86Rb+ efflux, demonstrating antagonism of alpha4beta2* nAChRs. Compared with lobeline, the defunctionalized analogs lobelane, mesotransdiene, and (-)-trans-transdiene showed dramatically reduced affinity at alpha4beta2* nAChRs and a 15- to 100-fold higher affinity (Ki = 1.95, 0.58, and 0.26 microM, respectively) at DATs. Mesotransdiene and (-)-trans-transdiene competitively inhibited DAT function, whereas lobelane and lobeline acted noncompetitively. 10S/10R-MEPP [N-methyl-2R-(2R/2S-hydroxy-2-phenylethyl)6S-(2-phenylethyl)piperidine] and 10R-MESP [N-methyl-2R-(2R-hydroxy-2-phenylethyl)6S-(2-phenylethen-1-yl)piperidine] were 2 to 3 orders of magnitude more potent (Ki = 0.01 and 0.04 microM, respectively) than lobeline in inhibiting [3H]serotonin uptake; 10S/10R-MEPP showed a 600-fold selectivity for this transporter. Uptake results using hDATs and human serotonin transporters expressed in human embryonic kidney-293 cells were consistent with native transporter assays. Lobelane and ketoalkene were 5-fold more potent (Ki = 0.92 and 1.35 microM, respectively) than lobeline (Ki = 5.46 microM) in inhibiting [3H]methoxytetrabenazine binding to VMAT2 in vesicle preparations. Thus, structural modification (defunctionalization) of the lobeline molecule markedly decreases affinity for alpha4beta2* and alpha7* nAChRs while increasing affinity for neurotransmitter transporters, affording analogs with enhanced selectivity for these transporters and providing new leads for the treatment of psychostimulant abuse.     

Device laboratory and postmortem parallels in alcoholic hepatitis during combined therapy using thioctic (alpha-lipoic) acid

The absence of clinical, biochemical, and instrumental signs that characterize the morphological pattern of the liver presents an urgent problem in the diagnosis of alcoholic hepatitis (AH). Sixty-one patients (mean age 41.7 +/- 8.7 years) were examined to study relationships between the histomorphological parameters and laboratory and instrumental findings in patients with AH on combined treatment including alpha-lipoic acid (Berlition). Indirect assessment of the histological activity of the disease may use the parameters of the serum activity of aspartate aminotransferase and gamma-glutamine aminotransferase, the stages of hepatic fibrosis-ultrasound symptoms: the splenic index at the early stages of the disease, the diameter of the splenic vein in moderate and severe fibrosis. The supplementation of Berlition in the combined therapy for AH decreases the severity of fatty hepatocytic dystrophy, hepatic inflammatory and necrotic changes, no increase or a decrease in the stage of fibrotic changes in the liver tissue.     

Changes in immunogenesis organs after thyroidectomy and hormonal correction in an experiment

Regulating effect of thyroid hormones on functions of organs of the immune system has been demonstrated in the experiment. Deficiency of thyroid hormones affects thymulin synthesis and morphofunctional status of immunogenesis organs. Combination of thymostimulin and thyroxin in the thyroidectomized animals, as compared to their separate use, is pathogenetically the most adequate correcting therapy aiming normalization of structural and functional disorders in the thymus and spleen. Prolonged reaction of tissual basophils saturated with heparin, indicated hormonal activation of blood anticoagulative system, and complex of the above hormones can be used for prevention of thromboembolic complications.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.     

Characteristics of non-Helicobacter pylori ulcer disease

AIM: To characterize clinicomorphological and psychosomatic manifestations of ulcer disease (UD) with reference to Helicobacter pylori (HP) contamination of gastric mucosa. MATERIAL AND METHODS: Out of 411 UD patients HP invasion was diagnosed in 338. RESULTS: Patients with UD having no HP in gastric mucosa showed clinical peculiarities related to changes in psychological and vegetative status. CONCLUSION: The addition of psychopharmacological drugs to conventional antiulcer therapy promoted induction of clinicoendoscopic remission of UD within optimal time and improved quality of life in patients without HP infection in the stomach.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

BACKGROUND: This study evaluated the usefulness of the serologic test for syphilis (STS) in preventing the transmission of human immunodeficiency virus (HIV), hepatitis B and C viruses, and human T- lymphotropic virus via the transfusion of seronegative, infectious window-period blood. STUDY DESIGN AND METHODS: Demographic and laboratory information on blood donations made between January 1992 and June 1994 in 18 American Red Cross regions was analyzed. It was assumed that the same proportion of HIV-positive and HIV-infectious window- period donations reacted on STS and were negative on other screening tests (hepatitis B and C viruses and human T-lymphotropic virus). This proportion multiplied by the estimated number of HIV-infectious window- period donations is the number of post-screening HIV-infectious donations removed by STS. RESULTS: Of 4,468,570 donations, 12,145 (0.27%) were STS positive and 377 (0.008%) were HIV positive. Among donations that were negative on other screening tests, STS-reactive donations were 12 times more likely to be HIV positive (odds ratio = 11.9; 95% CI = 5,26). However, of an estimated 13 infectious window- period donations, 0.2 would have been removed because of a reactive STS, at a cost of over $16 million. CONCLUSION: STS is a poor marker and a costly strategy for preventing post-screening HIV infections and other blood-borne diseases.